Abstract

Background

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, which includes
a spectrum of hepatic pathology such as simple steatosis, steatohepatitis, fibrosis
and cirrhosis. The increased serum levels of homocysteine (Hcy) may be associated
with hepatic fat accumulation. Genetic mutations in the folate route may only mildly
impair Hcy metabolism. The aim of this study was to investigate the relation between
liver steatosis with plasma homocysteine level and MTHFR C677T and A1298C polymorphisms
in Brazilian patients with NAFLD.

Methods

Thirty-five patients diagnosed with NAFLD by liver biopsy and forty-five healthy controls
neither age nor sex matched were genotyped for C677T and A1298C MTHFR polymorphisms
using PCR-RFLP and PCR-ASA, respectively, and Hcy was determined by HPLC. All patients
were negative for markers of Wilson’s, hemochromatosis and autoimmune diseases. Their
daily alcohol intake was less than 100 g/week. A set of metabolic and serum lipid
markers were also measured at the time of liver biopsies.

Results

The plasma Hcy level was higher in NAFLD patients compared to the control group (p = 0.0341).
No statistical difference for genotypes 677C/T (p = 0.110) and 1298A/C (p = 0.343)
in patients with NAFLD and control subjects was observed. The genotypes distribution
was in Hardy-Weinberg equilibrium (677C/T p = 0.694 and 1298 A/C p = 0.188). The group
of patients and controls showed a statistically significant difference (p < 0.001)
for BMI and HOMA_IR, similarly to HDL cholesterol levels (p < 0,006), AST, ALT, γGT,
AP and triglycerides levels (p < 0.001). A negative correlation was observed between
levels of vitamin B12 and Hcy concentration (p = 0.005).

Conclusion

Our results indicate that plasma Hcy was higher in NAFLD than controls. The MTHFR
C677T and A1298C polymorphisms did not differ significantly between groups, despite
the 677TT homozygous frequency was higher in patients (17.14%) than in controls (677TT = 4.44%)
(p > 0.05). The suggested genetic susceptibility to the MTHFR C677T and A1298C should
be confirmed in large population based studies.